There are significant clinical differences and outcomes between patients with systemic sclerosis (SSc)-mixed connective tissue disease (MCTD), SSc-overlap, and SSc-only, according to research results published in Arthritis Care and Research. Study investigators indicated better survival among patients with SSc-MCTD and SSc-overlap than among those with SSc-only.
Mixed connective tissue disease is defined by the presence of anti-ribonucleoprotein complex (RNP) antibody with >3 clinical features, including swollen fingers, synovitis, myositis, Raynaud phenomenon, or acrosclerosis. Patients diagnosed with SSc and with features of connective tissue diseases are typically classified as SSc-overlap.
To describe the clinical characteristics and outcomes of SSc-MCTD and SSc-overlap, 1728 patients (86% women; 95% white) from the Australian Scleroderma Cohort Study who met the American College of Rheumatology/European League Against Rheumatism criteria for SSc were enrolled in the study. A total of 5.6% (n=97) of patients were indicated to have both SSc and MCTD (SSc-MCTD), while 7.3% (n=126) were indicated to have SSc-overlap syndrome.
Researchers created 3 mutually exclusive groups, including SSc-MCTD (n=97), SSc-overlap (n=126), and SSc-only (consisting of the remaining 1505 patients). Mean duration of follow-up was similar between groups at approximately 4.5 years. Researchers performed univariate comparison of clinical features between groups using analysis of variance or chi-square, and conducted survival analysis using Kaplan-Meier curves and Cox regression.
Results of the study indicated that among patients with SSc-overlap, 38.9% had overlap with rheumatoid arthritis, 34.1% with Sjogren syndrome, 13.5% with systemic lupus erythematous, 17.5% with polymyositis, and 2.4% with dermatomyositis. Compared with patients in the SSc-overlap and SSc-only groups, patients with SSc-MCTD group were younger at disease onset (46.5 and 46.8 years vs 38.4 years, respectively; P <.0001). Patients in the SSc-MCTD or SSc-overlap groups were more likely than patients in the SSc-only group to have other positive autoantibodies, including anti-Ro, anti-La, anti-Jo-1, and antineutrophil cytoplasmic antibodies. Patients in the SSc-MCTD and the SSc-overlap groups had similar frequency of interstitial lung disease (ILD), whereas those in the group with SSc-MCTD had higher frequency of pulmonary arterial hypertension (PAH; 12.4% vs 4.8% and 11.1% in the SSc-overlap and SSc-only groups, respectively; P =.0751). Synovitis and myositis were equally common in the SSc-overlap and SSc-MCTD groups.
Patients with SSc-overlap were significantly more likely to have experienced dysphagia (60.3% vs 45.4% of SSc-MCTD vs 45.5% of SSc-only; P =.0006). Compared with patients in the SSc-only group, those in the SSc-MCTD and SSc-overlap groups had a higher likelihood of exposure to immunosuppressive treatment, including prednisolone and disease-modifying antirheumatic drugs.
Kaplan-Meier curves showed better survival in the SSc-MCTD group compared with patients in the SSc-overlap or the SSc-only groups (P =.011); however, scleroderma-specific antibodies that were more reliable indicators of survival indicated that antinuclear antibody-centromere or anti-RNP conferred consistently better survival than anti-topoisomerase 1 (Scl)-70 or anti-RNA polymerase 3. Researchers noted that compared with patients with SSc-only, those with SSc-MCTD or SSc-overlap had lower all-cause mortality after ILD and PAH diagnosis (P =.024). Overall, compared with SSc-only, SSc-MCTD and SSc-overlap groups combined had significantly better survival (P =.019).
Study limitations included survivor bias, retrospective analysis, and a small SSc-MCTD sample size for the subgroup analysis.
“This study provides insights into the clinical characteristics of patients with SSc-MCTD, SSc overlap, and SSc-only, and shows that anti-RNP antibodies are associated with better survival than anti-Scl-70 and anti-RNA polymerase  antibodies,” the researchers concluded.
Disclosure: Several study authors declared affiliations with the pharmaceutical industry. Please see the original reference for a full list of authors’ disclosures.
Fairley JL, Hansen D, Proudman S, Sahhar J, Ngian GS, Walker J. Clinical characteristics and survival in systemic sclerosis-mixed connective tissue disease and systemic sclerosis-overlap syndrome [published online February 14, 2020]. Arthritis Care Res. doi:10.1002/acr.24167